PRIMARY OBJECTIVE To determine the percentage of patients with high risk neuroblastoma in
first or subsequent partial response or better, or with microscopic residual bone marrow
disease, who demonstrate an immunological anti-tumor response at any time during, and for up
to 12 months from initiation of, treatment with subcutaneous injections of autologous
neuroblastoma cells, genetically modified by adenoviral vectors to secrete interleukin-2
(IL-2) (autologous neuroblastoma vaccine)
SECONDARY OBJECTIVES 1. To determine the toxicity of the autologous neuroblastoma vaccine
given according to this schedule 2. To obtain preliminary data on the effect of vaccine
administration on progression-free survival from high-risk neuroblastoma
Tumor cells from subjects with high-risk neuroblastoma will be obtained at the time of
presentation and initial diagnosis, during routine surveillance of bone marrow disease
status, or at the time of surgical resection of disease during primary chemotherapy. The
tumor cells will be irradiated to prevent the possibility of tumor growth. Autologous
neuroblastoma tumor cells will be used to treat neuroblastoma following the completion of
primary or salvage chemotherapy when peripheral blood lymphocyte counts have recovered to >
500 CD3+ cells/mm3. This preceding chemotherapy may or may not have included bone marrow or
peripheral stem cell rescue. Therefore, following the achievement of best response with
chemotherapy, vaccine will be administered for 6 months. Vaccine modified for secretion of
IL-2 will be used.
Vaccine therapy will commence after complete recovery from the side effects of primary or
salvage chemotherapy, as long as the subject has an absolute CD3+ lymphocyte count and an
absolute neutrophil count greater than 500/mm3. A vaccine consisting of 0.3 x 10 8
cells/patient will be given per injection, based on data from the Phase I studies.
Injections will be given twice monthly for two months, then monthly for four months, for a
total of eight vaccine injections over six months. The immune effects of the vaccine,
toxicity of treatment, and anti-tumor effects will be periodically assessed. Further
evaluation will be done annually.
The first and second vaccine injection sites will be "punch biopsied" one week after the
injection. Several x-rays and various types of scans will also be taken to assist with
monitoring the status of the neuroblastoma. Complete details of the evaluations required by
this study are included in.
Subjects may receive supportive care for any acute or chronic toxicity from the injections,
including blood product support, antibiotics, and other appropriate intervention.
Pneumocystis carinii prophylaxis initiated during chemotherapy may be continued during
vaccine therapy for as long as deemed appropriate by the investigator. As well, subjects
may receive concurrent therapy with cis-retinoic acid at the discretion of the treating
An adenoviral vector is being used to transduce the cells ex-vivo. Subjects will not be
treated with the viral vector.
- Patients with high risk neuroblastoma defined below, who, following completion of
front-line or salvage chemotherapy that may or may not have included high-dose
chemotherapy followed by peripheral blood stem cell or bone marrow rescue with or
without cis-retinoic acid, have achieved partial response or better, or who have
microscopic residual bone marrow:
1. INSS Stage 4 neuroblastoma, diagnosed between 1 and 21 years of age (inclusive)
2. INSS Stage 3, N-myc amplified neuroblastoma, diagnosed between 1 and 21 years of
3. INSS Stage 3, N-myc non-amplified, Shimada unfavorable histology neuroblastoma,
diagnosed between 1 and 21 years of age (inclusive)
4. INSS Stages 2A or 2B, N-myc amplified, Shimada unfavorable histology, diagnosed
between 1 and 21 years of age (inclusive)
5. INSS Stage 4 neuroblastoma, with Shimada unfavorable histology, diagnosed under
365 days of age
- Patients with intermediate or low risk neuroblastoma, who have achieved a second or
subsequent partial response or better following chemotherapy treatment of first or
- Patients must have recovered from the toxic effects of prior chemotherapy prior to
treatment on this study, and must have both an absolute lymphocyte count and an
absolute neutrophil count greater than 500/mm3.
- Patients with disease status outlined in the first bullet who have been treated with
allogeneic tumor vaccine are eligible for treatment with autologous tumor vaccine
when that product becomes available
- Patients may not concurrently receive any investigational agents or other tumor
- Patients must be HIV-negative.
- Female patients must not be pregnant or lactating.
- Patients must have autologous transduced neuroblastoma cells available that are
demonstrably producing > 150 pg IL-2/10e6 cells/24 hours.
- Patients or legal guardians must sign an informed consent according to institutional
- Patients who are sexually active must be willing to utilize one of the more effective
birth control methods during the study and for 3 months after the study is concluded.
The male partner should use a condom.